Triethylamine → HCID 11604752, compound

HRID 1881672Notes

Reaction equation

HRID 1881672 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)[N:9]=[CH:8][NH:7][C:6]2=O.P(Cl)(Cl)(Cl)=O.C(N(CC)CC)C.[Cl:36][C:37]1[CH:38]=[C:39]([CH:41]=[CH:42][C:43]=1[F:44])[NH2:40]>C(#N)C.C1(C)C=CC=CC=1>[Cl:36][C:37]1[CH:38]=[C:39]([CH:41]=[CH:42][C:43]=1[F:44])[NH:40][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 97083-Chloro-4-fluoroanilineHCID 24813Phosphorus oxychlorideHCID 1354371166-Methoxy-7-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 11604752HCID 11604752, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

In a 50 mL-volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.00 g (6.3 mmol) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one, 1.19 g (7.6 mmol) of phosphorus oxychloride, 0.76 g (6.3 mmol) of triethylamine, and 8 mL of toluene in a nitrogen atmosphere. The mixture was then stirred at 70-80° C. for 3 hours. Subsequently, the mixture was cooled to room temperature, and 1.09 g (6.3 mmol) of 3-chloro-4-fluoroaniline and 6 mL of toluene were added. The resulting mixture was stirred at 110° C. for 10 hours, Further, the mixture was stirred at room temperature after addition of 8 mL of acetonitrile. After the reaction was complete, the precipitated crystalline product was collected by filtration, and washed with 5 mL of cooled acetonitrile. Subsequently, the crystalline product was placed in 16 mL of aqueous sodium hydroxide (1 mol/L), and the aqueous mixture was stirred for 4 hours at room temperature. The crystalline product was collected by filtration, washed with 50 mL of water and 5 mL of acetonitrile, and dried under reduced pressure, to give 2.28 g (isolated yield: 71%, purity 89% in terms of area percentage determined by high performance liquid chromatography) of 4-(3-chloro-4-fluoroanilino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline as a sallowish crystalline product.

Workup

  1. customIn a 50 mL-volume glass vessel equipped with a stirrer
  2. temperatureSubsequently, the mixture was cooled to room temperature
  3. stirringThe resulting mixture was stirred at 110° C. for 10 hours
  4. stirringFurther, the mixture was stirred at room temperature
  5. filtrationthe precipitated crystalline product was collected by filtration
  6. washwashed with 5 mL of cooled acetonitrile
  7. stirringthe aqueous mixture was stirred for 4 hours at room temperature
  8. filtrationThe crystalline product was collected by filtration
  9. washwashed with 50 mL of water and 5 mL of acetonitrile
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-9f46176fe6c84b7eb9a7961c2899709e
Source dataset
uspto-grants-2012_11
Patent number
US08318932B2

Reaction notes

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